Article
Neurosciences
Dolores Piniella, Francisco Zafra
Summary: This article discusses the functions of NMDA-type glutamate receptors (NMDARs) in the central nervous system and their interaction with other endogenous ligands. The activity of NMDARs depends on the coincidental binding of glutamate with other cellular signals and is modulated by allosteric modulators such as zinc and protons. The GlyT1 transporter plays an important role in maintaining glycine concentration in the microenvironment of NMDARs. Although the inhibition of GlyT1 has been investigated as a treatment for schizophrenia, the results from phase III clinical trials have been disappointing. However, further research and the newly published 3D structure of GlyT1 may lead to the design of more effective drugs.
Article
Neurosciences
Amit Kumar, Ansab Akhtar, Anurag Kuhad, Sangeeta Pilkhwal Sah
Summary: This study found that sarcosine can alleviate the behavioral symptoms of schizophrenia by modulating oxidative stress, neuroinflammation, and mitochondrial dysfunction.
EXPERIMENTAL BRAIN RESEARCH
(2023)
Review
Environmental Sciences
Najm Alsadat Madani, David O. Carpenter
Summary: Glyphosate and glyphosate-based herbicides have adverse effects on nervous system function, including increased risk of Parkinson's disease and autism, impaired synaptic transmission through mechanisms such as oxidative stress and mitochondrial dysfunction. In addition, glyphosate-based herbicides alter the gut microbiome, which in turn affects susceptibility to neurological diseases.
ENVIRONMENTAL RESEARCH
(2022)
Review
Pharmacology & Pharmacy
Anna Pittaluga
Summary: This review summarizes the results from synaptosome studies over the past 40 years, supporting the existence of auto and hetero NMDA receptors controlling the release of transmitters in the CNS of mammals. Additionally, immunochemical studies in isolated nerve endings confirm these functional observations.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Daniel C. Javitt
Summary: Cognitive impairment is a prominent feature of schizophrenia, and its assessment methods are well established. The role of social cognitive impairment and sensory-level dysfunction in functional outcomes has also been recognized. Treatment development targeting N-methyl-d-aspartate receptor (NMDAR) and its associated impairments has become encouraging. Mismatch negativity has emerged as a promising biomarker for early-stage drug development in schizophrenia.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY
(2023)
Review
Neurosciences
Qiongqiong Wu, Jing Huang, Renrong Wu
Summary: The NMDAR hypofunction hypothesis offers a new perspective for treating negative symptoms and cognitive dysfunction in schizophrenia, with drugs targeting this receptor showing promise in improving symptoms. However, unsatisfactory outcomes in clinical studies suggest further research is needed to effectively utilize this hypothesis.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Psychiatry
Toral S. Surti, Mohini Ranganathan, Jason K. Johannesen, Ralitza Gueorguieva, Emma Deaso, Joshua G. Kenney, John H. Krystal, Deepak Cyril D'Souza
Summary: This study aimed to investigate the synergistic effects of a GLYT1 inhibitor and computerized cognitive training (CT) on cognitive impairments associated with schizophrenia (CIAS). However, the results showed that the combination of GLYT1 inhibitor with CT did not lead to greater improvement in CIAS compared to CT alone.
SCHIZOPHRENIA RESEARCH
(2023)
Article
Psychiatry
Uzma Zahid, Robert A. A. McCutcheon, Faith Borgan, Sameer Jauhar, Fiona Pepper, Matthew M. M. Nour, Maria Rogdaki, Martin Osugo, Graham K. K. Murray, Pamela Hathway, Robin M. M. Murray, Oliver D. D. Howes
Summary: This study found that baseline glutamatergic levels are unlikely to predict treatment response in patients with first episode psychosis. Antipsychotic treatment also does not significantly affect glutamate levels in the anterior cingulate cortex.
FRONTIERS IN PSYCHIATRY
(2022)
Article
Psychiatry
Anne S. Mallien, Natascha Pfeiffer, Miriam A. Vogt, Sabine Chourbaji, Rolf Sprengel, Peter Gass, Dragos Inta
Summary: Extensive evidence suggests dysfunction of NMDAR in schizophrenia may be related to early neurodevelopment, but clinical symptoms appear during late adolescence. NMDAR blockade/hypofunction can also trigger psychosis in adulthood without early neurodevelopmental issues. Deletion of NMDAR in late adolescence does not induce behavioral abnormalities resembling psychiatric disorders, indicating other neuronal substrates may underlie post-adolescent NMDAR-driven psychosis.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Chemistry, Medicinal
Pieter H. Bos, Evelyne M. Houang, Fabio Ranalli, Abba E. Leffler, Nicholas A. Boyles, Volker A. Eyrich, Yuval Luria, Dana Katz, Haifeng Tang, Robert Abel, Sathesh Bhat
Summary: The lead optimization stage of a drug discovery program involves the design, synthesis, and testing of numerous compounds. However, there are limitations to this process, including the difficulty of rapidly designing potent molecules and exploring a vast chemical space. To address these limitations, researchers have developed AutoDesigner, a novel algorithm that can generate and optimize millions to billions of virtual molecules while adhering to specific project criteria. The algorithm only requires a starting ligand and a binding model, making it suitable for early stages of drug discovery. The effectiveness of AutoDesigner was demonstrated by successfully designing novel inhibitors for d-amino acid oxidase and meeting various project goals.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Review
Neurosciences
David Stroebel, Laetitia Mony, Pierre Paoletti
Summary: Ionotropic glutamate receptors (iGluRs) are essential for excitatory neurotransmission in the vertebrate CNS and play a major role in learning and memory. Some iGluR subunits do not bind glutamate, but instead bind glycine and D-serine, which have different roles and affinities in various subtypes of glycinergic iGluRs. Glycine and D-serine influence the activity and function of iGluRs, reshaping our understanding of their signaling diversity and complexity in neuropharmacology.
Article
Environmental Sciences
Mohsen Shamsi, Maliheh Soodi, Shirin Shahbazi, Ameneh Omidi
Summary: The study found that Acetamiprid reduces glutamate levels, affects the expression of NMDA receptor subunits in the hippocampus, leading to impaired memory consolidation at low doses, and loss of neural cells in the dentate gyrus area at high doses.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2021)
Article
Clinical Neurology
Kah Kheng Goh, Tzu-Hua Wu, Chun-Hsin Chen, Mong-Liang Lu
Summary: In patients with schizophrenia, N-methyl-D-aspartate receptor modulator supplements, when used in conjunction with antipsychotic medications, can improve certain symptoms, particularly negative symptoms, with satisfactory side effects and safety profiles.
JOURNAL OF PSYCHOPHARMACOLOGY
(2021)
Article
Physiology
M. J. Olivares, A. Flores, R. von Bernhardi, J. Eugenin
Summary: Central respiratory chemoreceptors play a key role in maintaining respiratory homeostasis by sensing CO2 and H+ levels in the brain and activating the respiratory neural network. Glutamatergic neurons and astrocytes in specific brain regions, such as the RTN, contribute to this process by releasing ATP in response to hypercapnia and D-serine and glutamate as gliotransmitters.
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
(2021)
Article
Immunology
Md Abdul Alim, Mirjana Grujic, Paul W. Ackerman, Per Kristiansson, Pernilla Eliasson, Magnus Peterson, Gunnar Pejler
Summary: Mast cells play a role in communication between peripheral nerves and immune cells, expressing glutamate receptors and being sensitive to glutamate signaling. Glutamate induces upregulation of various glutamate receptors and gene expression in mast cells, including pro-inflammatory components and transcription factors. The presence of a functional glutamate-glutamate receptor axis in mast cells is supported by in vitro and in vivo evidence, revealing a novel principle of communication between immune cells and nerve cells.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Clinical Neurology
Xinghui He, Fan Chen, Yifan Zhang, Qing Gao, Yuguang Guan, Jing Wang, Jian Zhou, Feng Zhai, Detlev Boison, Guoming Luan, Tianfu Li
Review
Neurosciences
Detlev Boison, Jong M. Rho
Article
Cardiac & Cardiovascular Systems
Yong Wang, Yiming Xu, Siyuan Yan, Kaixiang Cao, Xianqiu Zeng, Yaqi Zhou, Zhiping Liu, Qiuhua Yang, Yue Pan, Xiaoling Wang, Detlev Boison, Yunchao Su, Xuejun Jiang, Vijay S. Patel, David Fulton, Neal L. Weintraub, Yuqing Huo
Summary: The study reveals a novel mechanism by which ADK promotes VSMC proliferation via inducing aberrant DNA hypermethylation, down-regulating KLF4 expression and promoting neointima formation. The findings suggest the possibility of targeting ADK as an epigenetic modulator to combat vascular injury.
CARDIOVASCULAR RESEARCH
(2021)
Review
Clinical Neurology
Devin K. Binder, Detlev Boison, Tore Eid, Wayne N. Frankel, Ana Mingorance, Bret N. Smith, Penny A. Dacks, Vicky Whittemore, Annapurna Poduri
Article
Cell Biology
Karolina Losenkova, Mariachiara Zuccarini, Marika Karikoski, Juha Laurila, Detlev Boison, Sirpa Jalkanen, Gennady G. Yegutkin
JOURNAL OF CELL SCIENCE
(2020)
Article
Neurosciences
Hai-Ying Shen, Landen Weltha, John M. Cook, Raey Gesese, Wakaba Omi, Sadie B. Baer, Rizelle Mae Rose, Jesica Reemmer, Detlev Boison
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2020)
Editorial Material
Dentistry, Oral Surgery & Medicine
Manvitha Kuchukulla, Detlev Boison
JOURNAL OF THE AMERICAN DENTAL ASSOCIATION
(2021)
Article
Neurosciences
Omar Ashraf, Trong Huynh, Benton S. Purnell, Madhuvika Murugan, Denise E. Fedele, Vineet Chitravanshi, Detlev Boison
Summary: SUDEP, a leading cause of death in patients with refractory epilepsy, is believed to be caused by centrally-mediated respiratory dysfunction. Research shows that seizures can trigger a surge in adenosine release, which suppresses breathing. Suppressing phrenic nerve activity may serve as a predictive biomarker for imminent SUDEP, allowing for timely intervention to potentially prevent SUDEP.
Review
Pharmacology & Pharmacy
Detlev Boison, Michael F. Jarvis
Summary: Adenosine kinase (ADK) is a widely expressed enzyme that regulates the concentration of adenosine and plays a crucial role in the endogenous protective effects of adenosine. Recent research has identified a potential role for the nuclear ADK isoform in epigenetic modulation, offering the possibility of developing novel ADK-isoform selective inhibitors.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Aarti Jagannath, Norbert Varga, Robert Dallmann, Gianpaolo Rando, Pauline Gosselin, Farid Ebrahimjee, Lewis Taylor, Dragos Mosneagu, Jakub Stefaniak, Steven Walsh, Teele Palumaa, Simona Di Pretoro, Harshmeena Sanghani, Zeinab Wakaf, Grant C. Churchill, Antony Galione, Stuart N. Peirson, Detlev Boison, Steven A. Brown, Russell G. Foster, Sridhar R. Vasudevan
Summary: Adenosine plays a crucial role in regulating circadian rhythms through multiple signaling pathways, influenced by sleep history and light exposure. These findings contribute to understanding the interaction between sleep and circadian timing.
NATURE COMMUNICATIONS
(2021)
Editorial Material
Neurosciences
Detlev Boison
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Neurosciences
Hoda Gebril, Amir Wahba, Xiaofeng Zhou, Tho Lai, Enmar Alharfoush, Emanuel DiCicco Bloom, Detlev Boison
Summary: The study found high levels of ADK-L expression during cerebellar development, which was maintained into adulthood. In the developing cerebellum, ADK-L was expressed in immature Purkinje cells and granular neuron precursors, while in adulthood, it was absent from Purkinje cells but widely expressed in mature granule neurons and their molecular layer processes. These findings suggest a functional role of ADK-L in the plasticity of the cerebellum.
Article
Biochemistry & Molecular Biology
Madhuvika Murugan, Denise Fedele, David Millner, Enmar Alharfoush, Geetasravya Vegunta, Detlev Boison
Summary: Adenosine kinase plays a crucial role in regulating adenosine metabolism and DNA methylation status through interactions with transmethylation reactions. The two isoforms of ADK have distinct subcellular localizations and may have different roles in epigenetic regulation. This review summarizes recent progress in understanding the biochemical interactions between ADK metabolism and epigenetic modifications.
NEUROCHEMISTRY INTERNATIONAL
(2021)
Review
Neurosciences
Edward Beamer, Manvitha Kuchukulla, Detlev Boison, Tobias Engel
Summary: Despite progress in understanding the pathogenesis of hyperexcitable networks and lowered seizure thresholds, treating epilepsy remains challenging. Many patients are resistant to current medications, which only provide symptomatic relief. Efforts are focused on finding new treatments with novel mechanisms of action to modify disease progression. Purines like ATP and adenosine play key roles in the epileptogenic process, with potential as targets for therapeutic strategies.
PROGRESS IN NEUROBIOLOGY
(2021)
Article
Chemistry, Medicinal
Amir E. Wahba, Denise Fedele, Hoda Gebril, Enmar AlHarfoush, Kiran S. Toti, Kenneth A. Jacobson, Detlev Boison
Summary: The study revealed that the adenosine kinase isoform ADK-L determines global DNA methylation levels in cancer cells, with the highest expression in HeLa cells. Inhibitors targeting ADK were found to significantly reduce global DNA methylation in HeLa cells, suggesting a potential therapeutic strategy for cancer treatment.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2021)
Article
Clinical Neurology
Hannah Meijs, Helena Voetterl, Alexander T. Sack, Hanneke van Dijk, Bieke De Wilde, Jan Van Hecke, Peter Niemegeers, Evian Gordon, Jurjen J. Luykx, Martijn Arns
Summary: This study used a polygenic score (PGS) and electroencephalography (EEG) data analysis to identify potential predictors for treatment outcomes in major depressive disorder (MDD). The results suggest the existence of a stable EEG network related to antidepressant-response that has potential as a predictor for MDD treatment, particularly in the case of venlafaxine.
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2024)
